William (Bill) C. Stanley (1957–2013)

Lopaschuk, Gary D.; Keehan, Kara Hansell; Taegtmeyer, Heinrich; Rosiers, Christine Des

doi:10.1152/ajpheart.00938.2013

Cited by 4 publications

(4 citation statements)

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“…Fatty acid oxidation is a major source of ATP from cardiac energy metabolism and the alteration of cardiac metabolism can reduce cardiac efficiency (Lopaschuk et al 2010). Cardiac mitochondrial metabolism-related proteins PGC1-α and CPT1 are essential proteins for the regulation of cardiac fatty acid oxidation (Duncan 2011, Lucas et al 2016.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury

Tanajak

Sa‐nguanmoo

Sivasinprasasn

et al. 2018

Journal of Endocrinology

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Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese insulin-resistant rats with/without cardiac I/R injury. The high-fat (HF) diet-induced obese insulin-resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa) and combination drugs (HFDaVil). At the end, I/R injury was induced by a 30-min left anterior descending coronary occlusion and 120-min reperfusion. Dapagliflozin showed a greater efficacy than vildagliptin in improving the metabolic impairments, low frequency/high frequency (LF/HF) ratio, systolic blood pressure and left ventricular (LV) function in comparison to HFV rats. In cardiac I/R injury, dapagliflozin had a greater efficacy than vildagiptin in decreasing mitochondrial DRP1, cleaved caspase 3, LV dysfunction and infarct size in comparison to HFV rats. However, the combined therapy showed the greatest efficacy in attenuating LV dysfunction, mitochondrial DRP1 and infarct size in comparison to HFV rats. In conclusion, dapagliflozin has a more pronounced effect than vildagliptin in obese insulin-resistant rats for the improvement of LV function. In rats with cardiac I/R injury, although dapagliflozin had a greater efficacy on cardioprotection than vildagliptin, the combined therapy exerted the highest cardioprotective effects potentially by reducing mitochondrial fission.

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Section: Discussionmentioning

confidence: 99%

Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury

Tanajak

Sa‐nguanmoo

Sivasinprasasn

et al. 2018

Journal of Endocrinology

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“…On the other hand, cardiac Akt is important for the translocation of GLUT-4 as Akt can also be activated by the insulin receptor (IR), leading to the inhibition of Akt substrate 160 (AS160), which then stimulates the translocation of GLUT-4-containing vesicles to the sarcolemma for the transport of glucose into cardiomyocytes (Sano et al 2003). However, a rapid shift from glucose to fatty acid metabolism occurs in the postnatal period, where thereafter fatty acids contribute ~70% of the total ATP generated (Lopaschuk et al 2010).…”

Section: Impact Of Iugr On Akt-mediated Metabolismmentioning

confidence: 99%

Akt signaling as a mediator of cardiac adaptation to low birth weight

Wang

Botting

Zhang

et al. 2017

Journal of Endocrinology

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Intrauterine insults, such as poor nutrition and placental insufficiency, can alter cardiomyocyte development, and this can have significant long-term implications for heart health. Consequently, epidemiological studies have shown that low-birth-weight babies have an increased risk of death from cardiovascular disease in adult life. In addition, intrauterine growth restriction can result in increased left ventricular hypertrophy, which is the strongest predictor for poor health outcomes in cardiac patients. The mechanisms responsible for these associations are not clear, but a suboptimal intrauterine environment can program alternative expression of genes such as cardiac IGF-2/H19, IGF-2R and ATR through either an increase or decrease in DNA methylation or histone acetylation at specific loci. Furthermore, hypoxia and other intrauterine insults can also activate the IGF-1 receptor via IGF-1 and IGF-2, and the AT receptor via angiotensin signaling pathways; both of which can result in the phosphorylation of Akt and the activation of a range of downstream pathways. In turn, Akt activation can increase cardiac angiogenesis and cardiomyocyte apoptosis and promote a reversion of metabolism in postnatal life to a fetal phenotype, which involves increased reliance on glucose. Cardiac Akt can also be indirectly regulated by microRNAs and conversely can target microRNAs that will eventually affect other specific cardiac genes and proteins. This review aims to discuss our understanding of this complex network of interactions, which may help explain the link between low birth weight and the increased risk of cardiovascular disease in adult life.

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“…Under basal conditions, fatty acids serve as major fuel substrates for energy production in the heart, but there is a metabolic switch in the ischaemic heart that leads to increased glucose utilization and glycolysis (Diaz et al, 1998;Stanley, 2001), similar to the fuel substrate switch that occurs in chronic hypoxia (induced by high altitude) (Essop, 2007). Glycolysis is also preferred to fatty acid utilization during the reperfusion because it is more oxygen-efficient (Lopaschuk and Stanley, 1997;Essop, 2007;Lopaschuk et al, 2010). ATP is mostly generated via oxidative phosphorylation under normal conditions in the cells, with only a small portion of ATP provided by glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post‐hypoxic cardiomyocytes

Gerö

Szabó

2015

British J Pharmacology

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BACKGROUND AND PURPOSEIschaemic heart disease can lead to serious, life-threatening complications. Traditional therapies for ischaemia aim to increase oxygen delivery and reduce the myocardial ATP consumption by increasing the coronary perfusion and by suppressing cardiac contractility, heart rate or blood pressure. An adjunctive treatment option for ischaemia is to improve or optimize myocardial metabolism. EXPERIMENTAL APPROACHMetabolic suppression in the ischaemic heart is characterized by reduced levels of high-energy molecules: ATP and NAD + . Because NAD + is required for most metabolic processes that generate ATP, we hypothesized that restoration of NAD + would be a prerequisite for ATP regeneration and examined the role of the major NAD + anabolic and catabolic pathways in the bioenergetic restoration process following oxygen-glucose deprivation injury in a cardiomyocyte cell line (H9c2 cells). KEY RESULTS Salvage of NAD+ via nicotinamide phosphoribosyl transferase was essential for bioenergetic recovery in cardiomyocytes. Blockade of nicotinamide phosphoribosyl transferase prevented the restoration of the cellular ATP pool following oxygen-glucose deprivation injury by inhibiting both the aerobic and anaerobic metabolism in the cardiomyocytes. NAD + consumption by PARP-1 also undermined the recovery processes, and PARP inhibition significantly improved the metabolism and increased cellular ATP levels in cardiomyocytes. CONCLUSIONS AND IMPLICATIONSWe conclude that the NAD + salvage pathway is essential for bioenergetic recovery in post-hypoxic cardiomyocytes and PARP inhibition may represent a potential future therapeutic intervention in ischaemic heart disease.

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William (Bill) C. Stanley (1957–2013)

Cited by 4 publications

References 0 publications

Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury

Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury

Akt signaling as a mediator of cardiac adaptation to low birth weight

Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post‐hypoxic cardiomyocytes

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